Bisphenol A activates Maxi-K (K Ca1.1) channels in coronary smooth muscle

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Abstract

Background and purpose: Bisphenol A (BPA) is used to manufacture plastics, including containers for food into which it may leach. High levels of exposure to this oestrogenic endocrine disruptor are associated with diabetes and heart disease. Oestrogen and oestrogen receptor modulators increase the activity of large conductance Ca 2+/voltage-sensitive K + (Maxi-K; K Ca1.1) channels, but the effects of BPA on Maxi-K channels are unknown. We tested the hypothesis that BPA activates Maxi-K channels through a mechanism that depends upon the regulatory β1 subunit. Experimental approach: Patch-clamp recordings of Maxi-K channels were made in human and canine coronary smooth muscle cells as well as in AD-293 cells expressing pore-forming α or α plus β1 subunits. Key results: BPA (10 μM) activated an outward current in smooth muscle cells that was inhibited by penitrem A (1 μM), a Maxi-K blocker. BPA increased Maxi-K activity in inside-out patches from coronary smooth muscle, but had no effect on single channel conductance. In AD-293 cells with Maxi-K channels composed of α subunits alone, 10 μM BPA did not affect channel activity. When channels in AD-293 cells contained β1 subunits, 10 μM BPA increased channel activity. Effects of BPA were rapid (<1 min) and reversible. A higher concentration of BPA (100 μM) increased Maxi-K current independent of the β1 subunit. Conclusions and implications: Our data indicate that BPA increased the activity of Maxi-K channels and may represent a basis for some potential toxicological effects.

Original languageEnglish
Pages (from-to)160-170
Number of pages11
JournalBritish Journal of Pharmacology
Volume160
Issue number1
DOIs
StatePublished - May 2010

Keywords

  • Endocrine disruptor
  • K 1.1
  • KCNMA1
  • KCNMB1
  • Large conductance Ca /voltage- sensitive potassium channel
  • Oestrogen
  • Penitrem A

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